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Mol Biol Cell. 2016 May 15;27(10):1606-20. doi: 10.1091/mbc.E15-09-0675. Epub 2016 Mar 23.

The SH3 domain of UNC-89 (obscurin) interacts with paramyosin, a coiled-coil protein, in Caenorhabditis elegans muscle.

Author information

1
Department of Pathology, Emory University, Atlanta, GA 30322.
2
Department of Biology, University of Konstanz, 78457 Konstanz, Germany.
3
Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, GA 30144.
4
Department of Pathology, Emory University, Atlanta, GA 30322 pathgb@emory.edu.

Abstract

UNC-89 is a giant polypeptide located at the sarcomeric M-line of Caenorhabditis elegans muscle. The human homologue is obscurin. To understand how UNC-89 is localized and functions, we have been identifying its binding partners. Screening a yeast two-hybrid library revealed that UNC-89 interacts with paramyosin. Paramyosin is an invertebrate-specific coiled-coil dimer protein that is homologous to the rod portion of myosin heavy chains and resides in thick filament cores. Minimally, this interaction requires UNC-89's SH3 domain and residues 294-376 of paramyosin and has a KD of ∼1.1 μM. In unc-89 loss-of-function mutants that lack the SH3 domain, paramyosin is found in accumulations. When the SH3 domain is overexpressed, paramyosin is mislocalized. SH3 domains usually interact with a proline-rich consensus sequence, but the region of paramyosin that interacts with UNC-89's SH3 is α-helical and lacks prolines. Homology modeling of UNC-89's SH3 suggests structural features that might be responsible for this interaction. The SH3-binding region of paramyosin contains a "skip residue," which is likely to locally unwind the coiled-coil and perhaps contributes to the binding specificity.

PMID:
27009202
PMCID:
PMC4865318
DOI:
10.1091/mbc.E15-09-0675
[Indexed for MEDLINE]
Free PMC Article

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